Objectives Determine the efficacy of a new chelating agent, succimer, to alleviate lead toxicity in monkeys and determine the endogenous sources of lead remobilized. Parallels clinical trials in children. Evaluates neurobehavioral, hematopoetic and other endpoints. There is a pressing need to validate the efficacy of chelation agents such as succimer not only to reduce body lead stores in young children but also to alleviate neurobehavioral and target organ toxicity. These questions are being addressed in a well established animal model of childhood lead exposure, the rhesus monkey. Various treatment groups compare effects of treatment vs. no treatment when lead exposure is terminated (one year postpartum) and when treatment is given concurrent with continued lead exposure (daily until 2 years postpartum). Potential toxicity of the chelating agent also is being evaluated. Lead administration begins at birth and is given daily at levels that maintain a target blood lead concentration of 35 g Pb/dl, the midrange of the exposure level being evaluated in human clinical trials of succimer. Monkeys receive three treatment regimes of succimer beginning at approximately 12, 16, and 18 months of age. The efficacy of succimer in reversing neurobehavioral deficits will be monitored using a broad range of behavioral tests administered over the course of the three chelation therapies and after completion of all chelations, the latter to evaluate the long term efficacy of succimer therapy on neurobehavioral processes. Lead-induced alterations in the heme biosynthetic pathway are used as a sensitive biomarker of systemic organ lead toxicity. An established stable-lead isotope technique is being used to determine the removal of lead from skeletal and soft tissue stores. K-X-ray fluorescence techniques will be used at 3 yrs of age to assess long-term changes in reduction of skeletal lead due to chelation in adolescent monkeys. Results of the studies should provide valuable interpretive scientific data concerning the efficacy of succimer to alleviate neurobehavioral and target organ toxicity in children.